Treatment of Hashimoto Encephalopathy
Hashimoto encephalopathy should be treated with high-dose corticosteroids as first-line therapy, with consideration of additional immunosuppressive treatments such as intravenous immunoglobulin (IVIg), plasmapheresis, or rituximab for steroid-refractory cases. 1, 2
First-Line Treatment: Corticosteroids
High-dose corticosteroids are the cornerstone of treatment for Hashimoto encephalopathy, with most patients showing rapid clinical improvement. 1, 3
- Start with high-dose oral steroids at 0.5-1 mg/kg/day of prednisolone or equivalent 1
- For acutely ill patients, consider intravenous methylprednisolone (1 gram daily for 3-5 days) followed by oral taper 3, 2
- Antibody levels typically normalize within 3-6 months of steroid therapy 1
- After initial response, taper steroids gradually over 12 months to prevent relapse 1
- Long-term maintenance immunosuppression may be necessary in some cases 3, 2
The British guidelines specifically recommend early immune suppression for antibody-mediated encephalitis, noting that delayed treatment results in poorer outcomes 1. This is critical because Hashimoto encephalopathy has been reclassified as steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), emphasizing its responsiveness to immunosuppression 2.
Second-Line Treatments for Steroid-Refractory Cases
If response to steroids is incomplete or the patient cannot tolerate prolonged steroid therapy, escalate to additional immunomodulatory treatments. 1, 4
Intravenous Immunoglobulin (IVIg)
- Dose: 0.4 g/kg/day for 5 days 1
- Can be used in conjunction with steroids to accelerate improvement 1
- May be less effective as monotherapy without concurrent steroids 1
Plasmapheresis
- Consider when high-dose steroids produce suboptimal clinical response 4
- Can achieve complete remission when steroids alone are insufficient 4
- Particularly useful in cases with persistent symptoms despite adequate steroid dosing 1
Rituximab (Anti-CD20 Therapy)
- Reserved for steroid-refractory cases, especially in pediatric patients 5
- Monoclonal antibody directed against CD20 on B cells 5
- Important caveat: Monitor immunoglobulin levels carefully, as low IgG levels are a significant side effect requiring vigilant surveillance 5
Diagnostic Confirmation Before Treatment
Before initiating immunosuppression, confirm the diagnosis by demonstrating elevated anti-thyroid antibodies (anti-thyroid peroxidase and anti-thyroglobulin) and excluding other causes of encephalitis. 1, 2
Key diagnostic features that should prompt consideration of Hashimoto encephalopathy include:
- Subacute presentation with confusion, seizures, or altered mental status 1, 2
- Hyponatremia (present in approximately 60% of cases) 1
- Elevated CSF protein with normal or mildly elevated cell count 3, 2
- Characteristic MRI findings showing hippocampal high signal (in 60% of cases) 1
- Presence of orofacial dyskinesia, choreoathetosis, or faciobrachial dystonic seizures 1
Critical exclusion: Rule out neuronal surface antibody-associated encephalitis (NMDA receptor, VGKC-complex) and infectious causes, as these require different management approaches 1, 2.
Thyroid Function Management
Address any concurrent thyroid dysfunction (hypothyroidism or hyperthyroidism), though the neurological symptoms respond to immunosuppression independent of thyroid status. 6, 2
- Most patients are in a subclinical hypothyroid state, but hyperthyroidism can occur 6, 2
- Treat thyroid dysfunction appropriately with levothyroxine or antithyroid medications as indicated 6, 2
- The encephalopathy responds to steroids regardless of thyroid function status 2
Tumor Screening
Screen all patients for underlying malignancy, particularly in cases with VGKC-complex or NMDA receptor antibodies, though tumors are less common in Hashimoto encephalopathy than in other antibody-mediated encephalitides. 1
- Perform appropriate imaging (CT chest/abdomen/pelvis, pelvic ultrasound in females) 1
- Thymoma and small cell lung cancer are the most common associated tumors when present 1
- Annual surveillance may be warranted in select cases 1
Common Pitfalls to Avoid
Do not delay steroid treatment while awaiting antibody results if clinical suspicion is high, as early intervention significantly improves outcomes 1. The British guidelines emphasize that antibody-mediated encephalitis has poor outcomes if untreated 1.
Do not assume this is an infectious encephalitis requiring only antimicrobials, even if fever and leukocytosis are present 4. Negative CSF microbiological testing with elevated thyroid antibodies should prompt immediate consideration of Hashimoto encephalopathy 4.
Do not use IVIg alone without steroids as first-line therapy, as this approach may be less effective at reducing antibody levels and achieving optimal clinical outcomes 1.
Special Consideration: IgG4-Related Disease
Be aware that a subset of patients, particularly younger males with very high thyroid antibody titers, may have IgG4-related Hashimoto encephalopathy, which represents a more aggressive form. 2